Acute Kidney Injury Associated With Late-Onset Neonatal Sepsis: A Matched Cohort Study

J Pediatrics. 2021, 231: 185-192. doi: 10.1016/j.jpeds.2020.12.023

SA Coggins, B Laskin, MC Harris, RW Grundmeier, Mm Passarella, KJ McKenna, L Srinivasan.

Reviewed by Alison Kent


Late onset sepsis occurs in 10-41% of neonates – depending on gestational age/birthweight. AWAKEN study observed prevalence of AKI among NICU patients of 30%. Neonatal sepsis may increase the risk of AKI due to altered haemodynamics, inflammation and nephrotoxic medications. Authors had previously identified an 8% incidence of new renal dysfunction in infants with culture proven sepsis. Another study showed a 40% incidence of AKI in those with fatal sepsis.

What was the purpose of the study?

The purpose of the study was to determine the incidence and severity of AKI within 7 days of late onset sepsis. Secondary aims were to assess the timing of AKI onset, duration and relationship with mortality within 30 days.

What were the study design and methods?

This was a matched retrospective cohort study at Children’s Hospital of Philadelphia. Neonates were included if they were investigated for sepsis after 72 hours of life. Study period was from January 2013 to December 2018. Sepsis cases were those who were investigated for sepsis with a positive culture from blood or CSF and received 5 or more days of treatment. Controls were considered those who were investigated for sepsis but had negative blood cultures and antibiotics for less than 48 hours. There was no crossover of patients between groups. AKI definition was nKDIGO – at least a 1.5 fold increase in SCr from established baseline, an increase of at least 0.5 mg/dL (44 mmol/L). Severe AKI was defined as stage 2 or 3 AKI with at least a doubling of baseline SCr.

What were the results of the study?

There were 4512 sepsis evaluations with 213 culture proven sepsis events (185 patients) that were matched to 213 controls. 203 cases and 193 controls had sufficient SCr data. There were more SCr measurements during evaluation period. The cases with sepsis had higher proportion with NEC, had significantly more vasopressor use in the 7 days before and after sepsis evaluation. Seven neonates in each group required ECMO.

20% of sepsis cases developed AKI in comparison to the 8% of controls. Stage 2 AKI occurred in 5.9% of sepsis cases and 2.6% of controls, and Stage 3 AKI in 5.4% of cases and 1% in controls.

There was no association with AKI and type of organism or nephrotoxic agents.

Most AKI episodes occurred within 48 hours of sepsis. 23% of sepsis cases did not have SCr return to baseline within 30 days and 13% of controls.

Risk factors for sepsis and AKI included increasing SCr by 0.1 mg/dL, increasing vasopressor days, history of NEC and ECMO. After adjustment for confounders, sepsis remained an independent risk factor for AKI.

Sepsis cases had a significantly higher 30 day mortality rate than controls (10% vs 4%) and last follow up (not defined in the paper) (29% vs 11%). AKI within 7 days of sepsis was associated with 30 day mortality (p=0.02) with severe AKI having even greater association with mortality (p=0.001).

What was the conclusion?

Culture proven sepsis in neonates has an increased risk for AKI and AKI severity. AKI was associated with increased mortality. Failure of SCr to return to baseline within 30 days was correlated with mortality. Prevalence of AKI is probably underappreciated as sepsis cases had more SCr measurements than controls.

Why does this matter?

This study shows that both sepsis evaluation and proven sepsis is associated with AKI, and that AKI with sepsis is an independent risk factor for mortality. A number of neonates did not have their SCr return to baseline within 30 days, which may place them at risk of future CKD. Infants with suspected sepsis should be evaluated for AKI in the 48 hours to 7 days after sepsis evaluation. A lack of routine inclusion of SCr with sepsis evaluation and electrolyte assessment likely reduces the detection of neonates with AKI.